P0663Comparative Effectiveness of Advanced Therapies between Ulcerative Proctitis and More Extensive Forms of Ulcerative Colitis: Results from a Multicenter Real-World Study

Abstract Background Most pivotal trials for advanced therapies in ulcerative colitis (UC) exclude patients with isolated rectal disease. This study compares treatment effectiveness between E1 (rectal) and E2/E3 (left-sided or extensive) UC. Methods This analysis pooled individual-level data from several multicentre, retrospective, real-world comparative studies. All consecutive patients with active disease (partial Mayo score (PMS) 2) who initiated an advanced therapy after failure of at least one biologic were included. The primary outcome was steroid-free symptomatic remission, defined as a PMS ≤ 2 at week 14 (W14). The comparison for the primary outcome was adjusted for potential confounders, including concomitant medications. The secondary outcome was discontinuation-free survival. A subgroup analysis of the primary outcome was performed within each therapeutic class. Results A total of 608 patients were included: 73 were E1 and 535 E2/E3. Among them, 48% were female, the median age was 39 years interquartile range: 27–54, and the median disease duration was 6 years 3–10. Overall, 38% of patients were initiating a second-line advanced therapy, 35% a third-line, 17% a fourth-line, and 4% a fifth-line treatment. The initiated drug was vedolizumab in 28% of cases, ustekinumab in 24%, and a JAK inhibitor (tofacitinib, filgotinib, or upadacitinib) in 48%. A concomitant treatment was prescribed in 256 patients (42%): 76 (13%) with 5-aminosalicylates, 55 (9%) an immunomodulator and 166 (27%) corticosteroids. E1 disease was not significantly associated with a different rate of symptomatic remission at week 14 in univariate analysis (OR = 1.50 95% CI: 0.94–2.89, p = 0.09). In the multivariate analysis adjusted for age, disease duration, baseline PMS, elevated baseline CRP, concomitant therapy, and number of prior treatment lines, disease extent was not associated with remission (OR = 1.75 0.87–3.70, p = 0.13). Conversely, an elevated PMS was independently associated with lower rates of remission (OR = 0.84 0.75–0.95, p = 0.004). Survival analysis showed no difference between the two groups in time to treatment discontinuation for failure (HR = 0.78 0.56–1.10, p = 0.20), Figure. Subgroup analyses by therapeutic class found no difference in efficacy according to disease extent, whether for vedolizumab (OR = 0.91 0.30–2.84), ustekinumab (OR = 1.81 0.32–14.32), or JAK inhibitors (OR = 2.63 0.94–10.0) (all non-significant). Conclusion In this large multicenter real-world cohort, advanced therapies demonstrated similar efficacy in patients with isolated rectal UC compared with those with more extensive disease, underscoring the need to adequately treat this disease location. Conflict of interest: Dr. Hupé, Marianne: Abbvie, Takeda, Celltrion Healthcare, Pfizer, Johnson & Johnson, Lilly, Amgen Uzzan, Mathieu: Grant: ECCO-IOIBD, Fondation pour la Recherche Medicale (FRM), SNFGE Personal Fees: Abbvie, Takeda, Celltrion, Janssen, Amgen, Alfasigma, Pfizer Altwegg, Romain: Advisory boards from Abbvie, Takeda, Johnson and Johnson, Lilly, Alphasigma, Celltrion, Pfizer, Amgen, Biogen, Sandoz, Ferring Bouguen, Guillaume: Grant: Abbvie, Ferisinus Personal Fees: Abbvie, Takeda, Fresinus, Amgen, Biogène, Arena, Ferring, Gilead, Janssen, MSD, Pfizer, Sandoz, Takeda, Tillots, Vifor pharma Nachury, Maria: Abbvie, Alfa Sigma, Biosynex, Celltrion, Galapagos, Janssen, Lilly, MSD, Pfizer, Takeda Domas, Quentin: No conflict of interest Fumery, Mathurin: Grant: Pfizer Personal Fees: Abbvie, Janssen, Takeda, MSD, Biogen, Amgen, Sandoz, Fresenius, Gilead, Celgene, Galapagos, Mylan, Tillots, Ferring, Pfizer, Hospira, CTMA, Boehringer, Lilly, Arena Non-financial Support: Abbvie, Janssen, Takeda, MSD, Galapagos, Ferring, Pfizer Tretón, Xavier: Personal Fees: Lectures and advisory board : Abbvie, Celltrion, MSD, Johnson & Johnson, Takeda, Amgen, Alphasigma, Lilly, Pfizer Other: participations: Thabor Therapeutics Amiot, Aurelien: Personal Fees: Abbvie, Fresenius-Kabi, Adacyte, Tillotts pharma, Janssen, Pfizer, Biogen, AMgen, Sandoz, Takeda, Galapagos, Eli Lilly Vuitton, Lucine: Abbvie, Amgen, Viatris, Celltrion, Janssen, Takeda, Lilly, Pfizer, Dr Falk Pharma, MSD, Ferring, Galapagos Caillo, Ludovic: Abbvie, Amgen, Celltrion, Ferring, Fresenius, Lilly, Jonhson & Jonhson, MSD, Pfizer, Takeda, Sandoz Gilletta de Saint Joseph, Cyrielle: Speaker/ consultant fees from Abbvie, AlfaSigma, Amgen, Celltrion, Ferring, Fresenius, Janssen, Lilly, Pfizer, Takeda and Tillots Pereira, Bruno: No conflict of interest Buisson, Anthony: Grant: Abbvie, Celltrion, Pfizer and Takeda Personal Fees: Abbvie, Amgen, Arena, Biogen, Celltrion, Ferring, Janssen, MSD, Pfizer, Roche, Sanofi-Aventis, Takeda, Tillotts, Vifor Pharma,